Our studies are directed primarily toward elucidating the mechanism of action of compounds which modulate gene action in murine virus-induced erythroleukemia cells. We continue to investigate the mechanism of action of biological response modifiers, since it is not understood how DMSO or a variety of unrelated compounds act to trigger the program of erythroid differentiation. During the past year, studies on Nabutyrate-treated murine virus-induced erythroleukemia cells revealed that they do not undergo the morphological alteration that usually accompany induction of differentiation. After 4 days of treatment with DMSO or HMBA, two potent inducers, most of the cells are committed to the erythroid pathway and proceed to terminal differentiation in the absence of the inducer. In contrast, we find cells treated with Nabutyrate "dedifferentiate" within 48 hrs after the inducer is removed from the medium, suggesting it may act through mechanisms different from those of DMSO and HMBA. No differences were detected, however, in the viral integration patterns nor in the number of viral copies/cell between the control untreated cells and the cells treated with only one of the three inducers studied. In our FLvac cells, which are dually infected with vaccinia virus, the pattern of retroviral integration and the expression of gp70, gp52, and gp30 do not appear to be altered. These cells remained responsive to induction, although vaccinia DNA sequences were detected in the nuclei of three out of four FLvac cell lines analyzed. Whether these sequences are integrated or in episomal forms is under study. We have also developed a new erythroleukemia cell line designated SQA. It originates from the leukemic spleen of an FLV-infected DBA/2J mouse and produces leukemogenic virus in contrast to our other permanent lines which produce attenuated virus. (M)